The long-range objective of this program is to study the mechanism of control of fatty acid synthesis in liver, a primary site for fatty acid, phospholipid and triacylglycerol synthesis. One of the major goals of future research is to isolate and purify (C14) acetyl, (C14) malonyl, and (C14) palmityl peptides belonging to the 'hydroxyl' transacylase site of chicken liver fatty acid synthetase. Isolation and purification is being carried out by high voltage electrophoresis and ion-exchange chromatography on Dowex 1-X2 and Dowex 50-X8. Sequence of these peptides is being planned as a part of future research. We also plan to delineate the nature of inhibition of fatty acid synthetase by malonyl CoA and diisopropyl-phosphofluoridate. These compounds inhibit the enzyme irreversibly. An understanding of the specificity and selectivity of this inhibition in terms of the partial reactions of fatty acid synthesis will be investigated by using acyl derivatives of N-acetyl cysteamine. Another objective of the next grant period is to characterize soluble antigen-antibody complexes between non-homologous antigens and antibodies and to attempt to isolate specific antigenic fragment(s) of chicken and rat liver enzymes. Molecular sieve chromatography and anion exchange chromatographic procedures are to be used in these studies. Studies on the isolation of fatty acid synthetase subunits by affinity chromatography will be continued. In addition, we plan to study the control of fatty acid synthetase biosynthesis by insulin and triiodothyronine in thyroidectomized and thyridectomized-diabetic animals and in the isolated liver cell preparations from these animals. BIBLIOGRAPHIC REFERENCES: Muesing, R.A., Lornitzo, F.A., Kumar, S. and Porter, J.W. (1975). Factors affecting the reassociation and reactivation of half molecular weight non-identical subunits of pigeon liver fatty acid synthetase. J. Biol. Chem. 250, 1814-1823. Kumar, S. (1975). Functional deacylases of pigeon liver fatty acid synthetase complex. J. Biol. Chem. 250, 5150-5158.